Anglesey had been won by either the Liberal Party or the Whigs at every election since 1784, until Thomas surpisingly gained it for Labour in 1918. He held onto it at the 1922 General Election, standing as an Independent. The result at the last General Election was as follows;

The Labour party selected Edward Thomas John to defend the seat. He had been Liberal MP for East Denbighshire from December 1910-18. John, a pacifist, had left the Liberals to stand unsuccessfully as a Labour candidate in 1918. He was a prominent Welsh Nationalist.

The Liberal candidate was again Sir Robert Thomas, the former Wrexham MP who had fought here at the 1922 General Election. Thomas was a ship and insurance broker. Thomas had been allied to Lloyd George and had stood as a National Liberal last time. Even though the Liberals nationally had been divided between followers of Asquith and Lloyd George, the local Liberals managed to unite behind Thomas.

Even though the Coalition Government between the National Liberals and the Unionists had ended, the local Unionists chose not to contest the seat in 1922. However, for the by-election, they decided to intervene and field their own candidate, Richard Owen Roberts. Roberts had stood for the Unionists at Anglesey in 1910. He was a Barrister and sat on the London County Council for Lewisham East.

Labour's campaign was supported by visits from national figures such as Arthur Henderson, and a host of Labour MPs from south Wales such as David Watts Morgan, Tom Griffiths, David Grenfell and T. I. Mardy Jones, as well as prominent Welsh nationalist figures such as future Liberal MP William John Gruffydd and Principal Thomas Rees. John called for Welsh Home Rule, even though it was not Labour party policy.

The good Liberal result spurred moves towards Liberal reunion at a national level. Within days, the two Liberal groups in the House of Lords decided to accept Viscount Grey as their leader in the Lords.